# Upregulated haptoglobin in classical monocytes serves as a diagnostic and immunological biomarker in myocardial infarction: a cross-sectional multi-omics study

**Authors:** Hongchen Xu, Huibin Pan, Chanjuan Mo, Xueqi Guo, Longfei Ji, Danfei Shi, Binyu Wang, Guodong Li, Yong Li

PMC · DOI: 10.3389/fimmu.2025.1707912 · Frontiers in Immunology · 2025-10-28

## TL;DR

This study identifies haptoglobin as a key biomarker for myocardial infarction, showing it is highly expressed in classical monocytes and has strong diagnostic potential.

## Contribution

The novel contribution is identifying haptoglobin's upregulation in classical monocytes as a reliable diagnostic and immunological biomarker for myocardial infarction.

## Key findings

- Haptoglobin (HP) is significantly upregulated in myocardial infarction with high diagnostic value (AUC=0.833).
- HP is highly expressed in classical monocytes of MI patients, validated by qPCR in clinical samples.
- HP is implicated in immune responses and ferroptosis, suggesting a role in the immune microenvironment of MI.

## Abstract

Myocardial infarction (MI) is one of the leading causes of death worldwide. Finding reliable diagnostic biomarkers and gaining a deeper understanding of their role in the immune microenvironment is of great significance for improving clinical prognosis.

This study integrated multiple datasets from GEO (GSE141512, GSE95368, GSE269269) and TCGA data, and used various bioinformatics methods such as weighted gene co-expression network analysis (WGCNA), immune cell infiltration analysis, and single-cell RNA sequencing analysis to screen key genes related to the occurrence and development of myocardial infarction. We initially validated the results using a proteomic dataset (GSE95368) and clinical samples analyzed by qPCR. Critically, the dysregulation and diagnostic value of Haptoglobin (HP) were further confirmed in multiple independent external cohorts (GSE66360, and others.), solidifying its reliability as a biomarker.

The study found that Haptoglobin (HP) is a key gene significantly upregulated in myocardial infarction, and it exhibits high diagnostic value (AUC=0.833) in the proteomic dataset (GSE95368). Single-cell sequencing analysis showed that HP is significantly highly expressed in classical monocyte of MI patients, and this finding was validated by qPCR experiments in clinically collected classical monocytes samples (p<0.05). Functional enrichment analysis implicated HP in immune responses and ferroptosis.

The HP gene is a potential diagnostic biomarker for myocardial infarction, and its specific high expression in classical monocytes implies a potential role in the pathological process of myocardial infarction by regulating the immune microenvironment. This study provides a new research direction for the diagnosis and immune-targeted therapy of myocardial infarction, and has important clinical translational value.

## Linked entities

- **Genes:** HP (haptoglobin) [NCBI Gene 3240]
- **Diseases:** myocardial infarction (MONDO:0005068)

## Full-text entities

- **Genes:** HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}
- **Diseases:** MI (MESH:D009203), death (MESH:D003643)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12602245/full.md

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Source: https://tomesphere.com/paper/PMC12602245